Epstein Benjamin J, Gums John G
Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville, Florida 32601, USA.
Drugs. 2005;65(14):1949-71. doi: 10.2165/00003495-200565140-00004.
The optimal pharmacological therapy of community-acquired pneumonia (CAP) is one of the most ardently debated issues in medicine. Presently, most guidelines recommend either a fluoroquinolone alone or dual therapy with a third-generation cephalosporin plus a macrolide in patients hospitalised with CAP, but few provide clinicians with specific considerations for selecting from these agents. Despite a similar spectrum of activity and favourable resistance patterns (for fluoroquinolones and third-generation cephalosporins) against CAP pathogens, there is emerging evidence that dual therapy may be superior to monotherapy in certain populations.In patients with non-severe CAP, the evidence supports the use of either monotherapy or dual therapy in most patients; however, patients with severe CAP or bacteraemic pneumococcal CAP experience improved survival when treated with dual therapy. It is unclear from this evidence if any specific combination of agents is the most effective, but the combination of a third-generation cephalosporin plus a macrolide is the most extensively studied. Dual therapy was superior to monotherapy irrespective of the susceptibility of the aetiological pathogen, thus insufficient antimicrobial spectrum does not explain the disparity. The most likely explanation for improved outcomes with dual therapy is the combined effect of optimised antimicrobial spectrum (including atypicals), decreased impact of resistance to a single agent and the immunomodulatory effects of macrolides. Increasing resistance in patients with non-severe CAP warrants the consideration of dual therapy and perhaps a reappraisal of agents usually reserved for second-line therapy, including doxycycline, in these populations as well. In light of the available evidence, dual therapy should be strongly considered in all patients with severe CAP, especially when complicated by pneumococcal bacteraemia.
社区获得性肺炎（CAP）的最佳药物治疗是医学领域中最具争议的问题之一。目前，大多数指南推荐在因CAP住院的患者中单独使用氟喹诺酮类药物或采用第三代头孢菌素联合大环内酯类药物进行双联治疗，但很少为临床医生提供从这些药物中进行选择的具体考量因素。尽管氟喹诺酮类药物和第三代头孢菌素对CAP病原体具有相似的活性谱和良好的耐药模式，但越来越多的证据表明，在某些人群中双联治疗可能优于单药治疗。在非重症CAP患者中，证据支持大多数患者采用单药治疗或双联治疗；然而，重症CAP患者或血行性肺炎链球菌CAP患者接受双联治疗时生存率会提高。从这些证据中尚不清楚是否有任何特定的药物组合是最有效的，但第三代头孢菌素联合大环内酯类药物的组合是研究最广泛的。无论病原体的易感性如何，双联治疗均优于单药治疗，因此抗菌谱不足并不能解释这种差异。双联治疗预后改善最可能的解释是优化抗菌谱（包括非典型病原体）的综合作用、对单一药物耐药性影响的降低以及大环内酯类药物的免疫调节作用。非重症CAP患者耐药性增加，这使得在这些人群中考虑双联治疗以及可能重新评估通常留作二线治疗的药物（包括多西环素）成为必要。根据现有证据，所有重症CAP患者，尤其是合并肺炎链球菌菌血症的患者，都应强烈考虑双联治疗。
